Regularizing predicted complexes by mutually exclusive protein-protein interactions

Protein complexes are key entities in the cell responsible for various cellular mechanisms and biological processes. We propose here a method for predicting protein complexes from a protein-protein interaction (PPI) network, using information on mutually exclusive PPIs. If two interactions are mutually exclusive, they are not allowed to exist simultaneously in the same predicted complex. We introduce a new regularization term which checks whether predicted complexes are connected by mutually exclusive PPIs. This regularization term is added into the scoring function of our earlier protein complex prediction tool, PPSampler2. We show that PPSampler2 with mutually exclusive PPIs outperforms the original one. Furthermore, the performance is superior to well-known representative conventional protein complex prediction methods. Thus, it is is effective to use mutual exclusiveness of PPIs in protein complex prediction.